Developing new weapons in the fight against cancer

Cancer causes some 13% of deaths worldwide. Of these deaths, some 90% are caused not by the original cancer, but by its spread to other parts of the body. These secondary cancers, known as metastases, are most often caused by 'circulating tumour cells' (CTCs) which escape from the primary tumour and travel around the body in the bloodstream. In the process, CTCs often undergo modifications that make them more resistant to treatment than the primary tumours.

Developing new weapons in the fight against cancer

Cancer causes some 13% of deaths worldwide. Of these deaths, some 90% are caused not by the original cancer, but by its spread to other parts of the body. These secondary cancers, known as metastases, are most often caused by 'circulating tumour cells' (CTCs) which escape from the primary tumour and travel around the body in the bloodstream. In the process, CTCs often undergo modifications that make them more resistant to treatment than the primary tumours.

Being able to capture and study CTCs would be of enormous benefit for research, to help understand the cells’ metabolism, how they colonise other organs and how they may respond to either existing or future drugs. Existing technologies, however, are unable to do this. They are only able to count CTCs in patients with advanced metastases.

This was the challenge the CAMINEMS project was set up to address in 2009. Supported by European Union (EU) funding, the three and a half year project brought together 9 partners from 5 EU Member States, with expertise in both clinical and technological areas. The aim was to create a tool for the effective screening and analysis of CTCs which could ultimately be developed to a sufficient degree of efficiency and cost-effectiveness that it could be put to practical use in day-to-day patient treatment.

The project consortium focused on achieving this by combining three emerging technologies – nanotechnology, optical technologies, and microfluidics (the exploitation of the way fluids behave when constrained to a very small scale) – in order to produce a tiny device which could analyse cancer cells from patients’ blood in a minimally-invasive way, and provide clinicians with currently unavailable information about the risk of metastatic relapse and the best therapy.

In the words of the CAMINEMS project coordinator, Dr Jean-Louis Viovy of the Curie Institute in Paris, the key to the project was contained in the microfluidics techniques. “Microfluidics is the equivalent for biology of microcircuits and microprocessors for the electronics industry,” he says. “It is a system that allows us to integrate in a single ‘chip’ many different operations that lead from the sample to the result,” he explains.

Using these techniques, the CAMINEMS consortium was able to develop a tool which was able, first of all, to capture rare tumour cells such as CTCs, and then to use nano-observation and cell culture techniques to analyse and understand these cells. Initial tests on very small clinical groups have already indicated that the new device is able to capture the cells with a greater degree of efficiency and purity than was previously possible. At the same time, the greatly improved quantity and quality of information that can be gathered about the cells opens up the possibility of more complex diagnosis and treatment of cancers. With cancers often behaving differently in different patients, and displaying different characteristics, the technology developed by CAMINEMS should allow clinicians to move closer to the ideal of personalised medical diagnosis and treatment. The more advanced a cancer is, the more difficult it is to treat. The new CAMINEMS technology could help detect sooner if a cancer is developing resistance to a treatment, and thus save precious months or years in switching to a new, more efficient one.

A further key breakthrough achieved in the system, stresses Dr Viovy, is its flexibility. Designed as a ‘self-assembly’ tool, it provides the user with a basic kit which allows specific biological elements to be switched in or out. The tool can thus be adapted according to whatever specific test the user wishes to conduct. “All the biology is contained in magnetic particles that we put in the system at the moment of operation. This means we can decide, case by case or patient by patient, which biological question we shall ask,” says Dr Viovy. The effect of this is to provide a system with greatly enhanced cost-effectiveness, able to closely follow the rapid evolution of targeted therapies.

Having created the system and established its effectiveness, says Dr Viovy, the next step is to develop a more ’user-friendly’ version, able to process more samples in a shorter time and so make it of practical value to clinicians. Work is now underway to develop a second-generation, pre-industrial prototype, and to find partners for its eventual commercialisation.